1. Measuring the impact of PMTCT programmes Nigel Rollins Department of Child and Adolescent Health and Development WHO

2. MONITORING AND EVALUATING THE PREVENTION OF MOTHER-TO-CHILD TRANSMISSION OF HIV A GUIDE FOR NATIONAL PROGRAMMES Preliminary Version for AIDS 2010

3. IMPACT data Used to evaluate overall effectiveness of interventions Often used for advocacy Needs to tell the bottom line

4. Data presented as 'Impact' of PMTCT interventions / programmes Process / Output data –PMTCT Cascade Number of pregnant women tested for HIV Number of HIV infected pregnant women started on ART/ARV prophylaxis –Non-HIV indicators Health system effects Immunisation rates Outcomes Infants –Transmission rate –No. infants infected annually –Transmissions averted –HIV-free survival Mothers –Mortality among HIV-infected mothers –Proportion of maternal deaths attributable to HIV –Life expectancy of HIV- infected mothers

5. Leading causes of death among women of reproductive age (15-44 yrs) World %Deaths(000s)CauseRank 19.2682HIV/AIDS 1 14.6516Maternal conditions 2 6.4228Tuberculosis 3 4.7168Self-inflicted injuries 4 3.7132Road traffic accidents 5 Source: Women and Health report, WHO, 2009

6. Maternal Mortality Trends, 1980-2008 Source: Hogan et al, 2010

7. The global impact of ART & PMTCT scale up on child outcomes 430,000 new paediatric infections in 2008 200,000 cumulative new HIV infections in children have been averted in the past 12 years UNAIDS, WHO AIDS epidemic update 2009 2

8. Transmission rates as a measure of PMTCT impact Transmission rate – 8.8% But only measured in 410 infants of the 658 (62%) mothers originally identified

9. DREAM study: HIV transmission in infants born to mothers on ART 1,220 live born infants –1,150 evaluable 1 months –RF0.8% –BF1.2% 6 months –RF0.8% –BF1.8% Concluded ART 'effective'

10. Challenges and limits of using infant transmission rates as a measure of PMTCT effectiveness Sampling bias if transmission only measured in those infants brought back to PMTCT services May omit infants of mothers who: –Become infected after 1 st HIV test –Who never attend ANC Modelled approaches do not necessarily reflect real life e.g. non-adherence New guidelines re. ARVs for BF will require approaches to track HIV transmission until 18-24 months As a 'single' indicator or target, does not reflect … –Maternal health and survival and benefits of interventions –Success, or failure of identifying and initiating treatment of infected infants and improved survival –Potential for improved survival if ARVs enable safer BF

11. Average Change between Pre- PEPFAR era and PEPFAR era, CI Comparison of Average Change between Focus and Control, CI P-value Focus-3.18 (-5.50, -0.86)*1.61(-2.21, 5.42)P=.246 Control-4.79(-6.28, -3.29)* Shen. MOAE0101. IAS 2010 Another way of telling the story …

12. Mean Change between Pre- PEPFAR era and PEPFAR era, CI Comparison of Mean Change between Focus and Control, CI* P-value Focus-10.76 (-13.49, -8.03 )*-5.14(-0.63, -9.66)*P=.0028 Control-5.62(-7.40, -3.83)* Shen. MOAE0101. IAS 2010

13. Under-2 mortality – measured through a demographic surveillance system Ndirangu. AIDS 2010 In the context of a comprehensive programme offering ART to mothers and ARVs for prevention of MTCT including support for appropriate infant feeding practices, mainly BF

14. Infant and Child mortality rates – measured through a demographic health survey 50% increase in IMR/CMR despite <4% transmission 50% increase in IMR/CMR despite <4% transmission Higher infant and young child mortality (x 1.6) in rural areas where 45% of the populations lives (BFHS 2007) (BDS 2006, BFHS 2007)

15. J Acquir.Immune.Defic.Syndr. 2010;53(1):28-35 Decreased survival among infants who stopped BF early or who were never BF. AHR = 6.19; ( 95% CI 1.41–27.0, P = 0.015) 97% infants were tested at 6 wks – none infected. Difference was independent of maternal health or if receiving ART

16. East Africa Proportion of HIV-related under-5 mortality in African sub-regions, 1990-2007 Central Africa West Africa 1990199119921993199419951996 1997 1998199920002001200220032004200520062007 Proportion (%) 25 20 15 10 5 0 199019911992199319941995199619971998199920002001200220032004200520062007 Proportion (%) 25 20 15 10 5 0 Southern Africa 19901991 1992 199319941995 1996 19971998 1999 2000 20012002 20032004 20052006 2007 Proportion (%) 25 20 15 10 5 0 1990 19911992199319941995 1996 199719981999 20002001 2002 20032004 2005 20062007 Proportion (%) 25 20 15 10 5 0

17. Challenges and limits of using infant / child mortality as a measure of PMTCT effectiveness Demographic surveillance systems reflect population effects (universal coverage) but cannot be generalized as a measure of national impact Demographic health surveys are large scale national initiatives but difficult to repeat regularly in order to assess progress The prevalence of HIV will influence whether HIV- related mortality will ever contribute significantly to national mortality rates esp. in low prevalence settings

18. HIV free survival or a proxy … to reflect both transmission and survival To have children of mothers known to be HIV-infected survive while remaining HIV uninfected is the top priority The success of PMTCT activities, including cost-effectiveness, needs to be measured in terms of HIV-free survival and not just transmissions averted

19. Impact assessments Meaningful –Tells the full story Measurable –?HIV-FS Population-based. –Achieving 'Universal coverage'. Robust –Snapshots ……. Trends Replicable within a reasonable timeline –Within country or district health systems –Between countries Relevant for high and low prevalence settings

20. Recent approaches Identified HIV-free survival as the most important outcome but recognised that difficult to measure outside of cohorts and clinical studies –Require several years to establish cohorts in a specific population

21. Recent approaches Cord blood samples Transmission rates and presence of NVP / AZT

22. Using attendance at immunisation clinics to assess infant 6 week HIV prevalence and estimate trends in infant mortality rates If immunisation attendance is high, then = a proxy for population vertical transmission rates and major effects of HIV and PMTCT interventions on infant outcomes Dried blood spots requested from all infants attending 6 week immunisation clinics DBS tested for HIV antibodies (maternal) = infant exposure Where antibodies detected, same sample tested for HIV by DNA PCR = infant infection All mothers interviewed about deaths in other children Other information e.g. ARVs taken can also be captured In 2009, KZN DoH assessed 6 Districts, 347 clinics –38,113 interviews, 8013 DBS samples from infants 6wk old –Funded through GFATM Lancet 2002; 360:389 AIDS 2007;21(10):1341-1347 AIDS 2009;23(14):1851-7

23. Maternal HIV prevalence (DBS antibodies) Districtn = number infants tested ELISA +ve = HIV exposed %95% confidence interval 1. (Amjb)124146637.6 30.6 – 45.1 2. (Etkw)181284946.9 41.5 – 52.3 3. (Ug)121346538.3 35.3 – 41.4 4. (Umg)123654444.9 41.1 – 48.7 5. (Umk)128345335.2 31.5 – 39.1 6. (Zld)123044936.7 32.4 – 41.2 TOTAL8013323740.4 38.3 – 42.5 Impact KZN 2009. http://crh.ukzn.ac.za

24. HIV transmission rate by district DistrictNumber HIV infected mothers = infant HIV antibody +ve % of HIV infected infants (6wks) by HIV PCR +ve Transmission rate % (95% confidence intervals) 1. (Amjb) 4594.42.9 – 6.4 2. (Etkw) 83110.17.3 – 13.8 3. (Ug) 4646.04.2 – 8.5 4. (Umg) 5544.53.0 – 6.8 5. (Umk) 4518.05.4 – 11.6 6. (Zld) 4457.44.8 – 11.3 KZN TOTAL 3204*7.09.– 8.4 *excludes 33 babies where PCR result not obtained due to insufficient sample Impact KZN 2009. http://crh.ukzn.ac.za

25. HIV transmission rates by PMTCT regimen Maternal PMTCT regimen Number HIV infected mothers = infant HIV antibody +ve Transmission rate % 95% confidence intervals None32015.011.5- 19.3 NVP only25913.58.9 – 20.1 NVP and AZT21495.64.6 – 6.8 ART4025.03.2 – 7.6 Total31967.05.9 – 8.4 Impact KZN 2009. http://crh.ukzn.ac.za

26. Infant mortality rates 1997- 2007 Year No of births reported No of deaths aged<12 mths IMR95% CI 19971666442620.3 – 34.3 19981865412215.9 – 30.4 19992010542720.7 – 34.7 200026591003830.8 – 45.8 20012428903729.9 – 45.9 200228181194235.4 – 50.2 200330181555143.8 – 60.1 200434041865547.3 – 63.1 200536332145951.8 – 66.9 200630652377768.7 – 87.0 Impact KZN 2009. http://crh.ukzn.ac.za

27. Results: Infant mortality rate by district DistrictNumber of previous births: 2005-2007 Number of deaths IMR per 1000 live births 95% CI 1. (Amjb) 1048898470.7 – 101.7 2. (Etkw) 19401658572.8 – 99.1 3. (Ug) 1124887860.6 – 100.5 4. (Umg) 900475239.7 – 68.3 5. (Umk) 14761097362.7 – 86.7 6. (Zld) 12801038062.6 – 102.9 Total 77686017771.1 – 84.1 Impact KZN 2009. http://crh.ukzn.ac.za

28. Same methodology applied in a community- based evaluation 4258 households visited Number of children <18mo tested for HIV w/ evaluable EIA - 889/912 (97.5%) 58/885 (6.6%) HIV-infected by PCR IMR 67/1000 LB –36% at home

29. East Africa Proportion of HIV-related under-5 mortality in African sub-regions Central Africa West Africa 1990199119921993199419951996 1997 1998199920002001200220032004200520062007 Proportion (%) 25 20 15 10 5 0 199019911992199319941995199619971998199920002001200220032004200520062007 Proportion (%) 25 20 15 10 5 0 Southern Africa 19901991 1992 199319941995 1996 19971998 1999 2000 20012002 20032004 20052006 2007 Proportion (%) 25 20 15 10 5 0 1990 19911992199319941995 1996 199719981999 20002001 2002 20032004 2005 20062007 Proportion (%) 25 20 15 10 5 0 Low vs. high prevalence settings Consider IMR restricted to HIV-exposed infants

30. Maternal AIDS Free survival Rate of progression from delivery Kesho Bora. Th LB B105. Vienna IAS. 2010 12.4% 19.6%

31. Implication for evaluating the cost benefit of PMTCT investment Cost : benefit analyses of PMTCT investments should reflect the lifetime gains of mothers and infants surviving while being AIDS- or HIV-free and the interaction between the two –Putting a value only on infant transmissions averted underestimates the investment Strengthens the argument and justification for HIV investment as a contribution to achieving MDGs 4 and 5

32. Conclusions Impact assessments need to reflect the full scope of what PMTCT aims to achieve Robust, simple, combined methods are available but need investment to perform Impact assessments need to be repeated to monitor progress towards targets and to hold global and national authorities accountable for investments made/needed WHO is developing protocols for national or sub- national impact assessments